Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats

作者：Gomez Elodie; Schwendemann Cedric; Roger Severine; Simonet Serge; Paysant Jerome; Courchay Christine; Verbeuren Tony J; Feletou Michel^*

来源：American Journal of Physiology - Heart and Circulatory Physiology, 2008, 295(5): H2198-H2211.

DOI：10.1152/ajpheart.00507.2008

• smooth muscle
• prostacyclin receptor
• endothelium-derived contracting factors
• endothelial dysfunction
• spontaneously hypertensive rats
• Wistar-Kyoto rats

Gomez E, Schwendemann C, Roger S, Simonet S, Paysant J, Courchay C, Verbeuren TJ, Feletou M. Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats. Am J Physiol Heart Circ Physiol 295: H2198-H2211, 2008. First published September 26, 2008; doi: 10.1152/ajpheart.00507.2008.-In spontaneously hypertensive rat (SHR) aorta, prostacyclin is an endotheliumderived contracting factor contributing to the endothelial dysfunction. This study was designed to determine whether the impairment of the prostacyclin response is influenced by aging and whether such a dysfunction is observed in platelets. Isometric tension was measured in aortic rings, and aggregation was studied in platelet-rich plasma taken from 3-, 6-, and 15-mo-old Wistar-Kyoto rats (WKY) and SHR. In aorta from 3- and 6-mo-old WKY, prostacyclin and beraprost [prostacyclin receptor (IP) agonists] produced relaxations that were enhanced by Triplion (thromboxane-prostanoid receptor antagonist). In 15-mo-old WKY, the relaxations to beraprost were maintained, but not those to prostacyclin. In SHR aorta, prostacyclin or beraprost produced no or minor relaxations, which, in younger SHR, were enhanced by Triplion. In both strains, the relaxations were inhibited by CAY-10441 (IP receptor antagonist). The relaxations to forskolin and isoproterenol were reduced with aging. When compared with those of WKY, the relaxations to isoproterenol were reduced in 3- but not in 6- or 15-mo-old SHR, whereas those to forskolin were consistently diminished at any given age. Whatever the age, prostacyclin and beraprost produced CAY-10441-sensitive inhibitions of ADPinduced platelet aggregation. Both agonists were more potent in SHR than in WKY. Therefore, in platelets from WKY and SHR, the IP receptor-dependent antiaggregant response is functional and maintained during aging. In aorta from WKY those responses are reduced by aging and, in SHR, are already compromised at 3 mo. This dysfunction of the IP receptor is only partially explained by a general dysfunction of the adenylate cyclase pathway.

• 出版日期2008-11